The overall goal is to develop and apply new methods based on recombinant adenovirus mediated gene transfer a) for the study of the molecular mechanisms involved in synaptic vesicle release; b) specifically to define the roles of the N-ethylmaleimide-sensitive fusion protein (NSF) and of SNAP (soluble NSF attachment proteins) in synaptic transmission and plasticity. Specific Aims 1. To develop and use recombinant adenovirus mediated gene transfer to express dominant negative mutants and/or antisense ribozymes to NSF and alpha-SNAP. 2. By virus infection, to introduce these inhibitory components into hippocampal neurons in culture and in hippocampal organotypic slices. 3. To apply electrophysiological analysis to determine their effects on synaptic transmission.